BRC-supported research from the Francis Crick Institute and UCL has identified 14 proteins in the blood that can predict lung cancer risk more than five years before diagnosis.
The research, funded by Cancer Research UK, means that people at higher risk of developing lung cancer and might benefit from drugs to prevent lung cancer taking hold could be identified early – a major step towards precision cancer prevention.
The study, published in the journal Cell, involved analysis of blood samples from more than 48,000 people in the UK Biobank using machine learning. Along with age, smoking status and previous history of lung disease, the team identified 14 key proteins in the blood that could predict a future diagnosis of lung cancer. The team validated these proteins in eight datasets from across the world, finding that it was higher in patients who, in the future, developed lung cancer.
Analysis of the protein signature suggested that it does not come from the tumour itself, but reflects an altered inflammatory lung environment that precedes cancer. This previous inflammation could come about as a result of factors such as air pollution or cigarette smoke.
Earlier work by the team showed that pollution can activate damaged cells carrying cancer-causing mutations. The latest study found that pollution increased both the protein signature and the number of abnormal lung cells linked to early cancer development.
The study suggests that drugs which block the action of an inflammatory molecule called IL-1β could help prevent lung cancer in people with the high-risk protein signature.
Tej Pandya, Clinical PhD Student at UCL and visiting scientist at the Francis Crick Institute, said: “We've shown that the signature reflects an altered inflammatory lung environment before cancer takes hold. It's a proof of concept that, one day, we could use this signature to offer preventive treatment to people at risk of lung cancer.”
The work is part of the landmark TRAcking Cancer Evolution through therapy (Rx) (TRACERx) lung cancer studies, led by UCLH medical oncologist and UCL scientist Professor Charles Swanton.
Prof Swanton, who is Clinical Research Director and Principal Group Leader at the Crick and lead investigator for TRACERx, said: “Drugs like statins have transformed the prevention of cardiovascular disease, used to treat individuals with a high ‘low density lipoprotein’ (LDL). But we don’t yet have an LDL-like marker of risk or a statin for lung cancer. In the clinic, we see first-hand the impact of diagnosing lung cancer at a late stage, so being able to identify people at greater risk and intervene before the disease develops is critical.
“Finding a signal for an inflammatory state in the lungs has given us insight into this window of opportunity, when preventative treatment could work best. This work supports a relatively new idea in the field, that some common age-related diseases, causing a high burden of disease in the community, share a common, presymptomatic state of inflammation. We think the signature could in the future help to predict and help prevent lung cancer and other lung diseases.”
Read the press release from the Francis Crick Institute.
Image credit: Adobe Stock / utah51
